Characterization of two antimicrobial peptides produced by a halotolerant Bacillus subtilis strain SK.DU.4 isolated from a rhizosphere soil sample

A bacterial strain producing two antimicrobial peptides was isolated from a rhizosphere soil sample and identified as Bacillus subtilis based on both phenotypic and 16S rRNA gene sequence phylogenetic analysis. It grew optimally up to 14% NaCl and produced antimicrobial peptide within 24 h of growth. The peptides were purified using a combination of chemical extraction and chromatographic techniques. The MALDI-TOF analysis of HPLC purified fractions revealed that the strain SK.DU.4 secreted a bacteriocin-like peptide with molecular mass of 5323.9 Da and a surface-active lipopeptide (m/z 1056 Da). The peptide mass fingerprinting of low-molecular-weight bacteriocin exhibited significant similarity with stretches of secreted lipoprotein of Methylomicrobium album BG8 and displayed 70% sequence coverage. MALDI MS/MS analysis elucidated the lipopeptide as a cyclic lipopeptide with a β-hydroxy fatty acid linked to Ser of a peptide with seven α-amino acids (Asp-Tyr-Asn-Gln-Pro-Asn-Ser) and assigned it to iturin-like group of antimicrobial biosurfactants. However, it differed in amino acid composition with other members of the iturin family. Both peptides were active against Gram-positive bacteria, suggesting that they had an additive effect

AAV-based gene delivery of antimicrobial peptides to combat drug-resistant pathogens.

Antimicrobial peptides (AMPs) have emerged as potential alternatives to conventional antibiotics due to their novelty and multiple mechanisms of action. Because they are peptides, AMPs are amenable to bioengineering and suitable for cloning and expression at large production scales. However, the efficient delivery of AMPs is an unaddressed issue, particularly due to their large size, possible toxicities, and the development of adverse immune responses. Here, we have reviewed the possibilities of adeno-associated virus (AAV)-based localized gene delivery of AMPs for the treatment of infectious diseases with a special focus on respiratory infections. By discussing the gene delivery mechanism of AAV and the accompanying technical and therapeutic challenges with AMPs, we describe a foundation that emphasizes the use of viral vector-based gene delivery of AMPs for disease treatment

Synergy Pattern of Short Cationic Antimicrobial Peptides Against Multidrug-Resistant Pseudomonas aeruginosa

With the rise of various multidrug-resistant (MDR) pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes and alternative strategies is a major priority. Antimicrobial peptides (AMPs) cannot only kill MDR bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with polymyxin B, piperacillin, ceftazidime, cefepime, meropenem, imipenem, tetracycline, erythromycin, kanamycin, tobramycin, amikacin, gentamycin, and ciprofloxacin. In total, 403 unique combinations were tested against an MDR Pseudomonas aeruginosa isolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and polymyxin B, erythromycin, and tetracycline were found to be synergistic. Novel variants of indolicidin also showed a high frequency in synergist interaction. Single amino acid substitutions within the peptides can have a very strong effect on the ability to synergize, making it possible to optimize future drugs toward synergistic interaction

Pre-formulation and delivery strategies for the development of bacteriocins as next generation antibiotics

peer-reviewedBacteriocins, a class of antimicrobial peptide produced by bacteria, may offer a potential alternative to traditional antibiotics, an important step towards mitigating the ever increasing antimicrobial resistance crisis. They are active against a range of clinically relevant Gram-positive and Gram-negative bacteria. Bacteriocins have been discussed in the literature for over a century. Although they are used as preservatives in food, no medicine based on their antimicrobial activity exists on the market today. In order to formulate them into clinical antibiotics, pre-formulation studies on their biophysical and physicochemical properties that will influence their activity in vivo and their stability during manufacture must be elucidated. Thermal, pH and enzymatic stability of bacteriocins are commonly studied and regularly reported in the literature. Solubility, permeability and aggregation properties on the other hand are less frequently reported for many bacteriocins, which may contribute to their poor clinical progression. Promising cytotoxicity studies report that bacteriocins exhibit few cytotoxic effects on a variety of mammalian cell lines, at active concentrations. This review highlights the lack of quantitative data and in many cases even qualitative data, on bacteriocins’ solubility, stability, aggregation, permeability and cytotoxicity. The formulation strategies that have been explored to date, proposed routes of administration, trends in in vitro/in vivo behaviour and efforts in clinical development are discussed. The future promise of bacteriocins as a new generation of antibiotics may require tailored local delivery strategies to fulfil their potential as a force to combat antimicrobial-resistant bacterial infections

Notch signaling: A potential target for the development of host-directed therapies against tuberculosis

Tuberculosis (TB) is one of the preeminent causes of death among infectious diseases and remains a global threat to human health. Mycobacterium tuberculosis (Mtb) has coevolved with the human host and is an extremely successful pathogen by abusing the human system in different ways. Interestingly, Mtb can remain undetected in the human host for years as latent TB, so there is an urgent need to develop new therapies to combat Mtb. In the recent past, host-directed therapies have attracted the research community as a promising approach to combat TB, and thus novel host targets are of interest. In the present editorial, we have explored and suggested Notch signaling as a potential host target to develop a new therapeutic strategy against Mtb.</jats:p

Antimicrobial Peptides: An Emerging Hope in the Era of New Infections and Resistance

Recently, antimicrobial peptides (AMPs) have garnered significant attention as a viable alternative to traditional antibiotics [...